With regard to patients suffering from neurological or psychiatric diseases, e.g. Morbus Parkinson, essential tremors, dystonia, functional interferences following a stroke, migraine, obsessive-compulsive disorder, epilepsy, tinnitus, schizophrenia, depression, borderline personality disorders such as well as irritable bowel syndrome, groups of neural cells are active in described regions of the brain in a pathological synchronous way. In this case a large number of neurons form synchronous action potentials, this means the associated neurons stimulate excessively synchronously. In contrast to this the neurons of healthy people trigger in a qualitatively different way in these regions of the brain, e.g. in an uncorrelated manner.
Having regard to Morbus Parkinson the pathological synchronous activity in the thalamus and in the basal ganglia changes the neuronal activity in different regions of the brain e.g. in regions of the cerebral cortex, such as the primary motor cortex. In this connection the pathological synchronous activity in the region of the thalamus and the basal ganglia, for example, impinges its rhythm onto the regions of the cerebral cortex in such a way that finally the muscles controlled by the regions develop a pathologic activity, e.g. a rhythmic tremor. Having regard to chronic subjective tinnitus, the pathological synchronous activity takes place in a network of auditory as well as non-auditory regions of the brain.
Having regard to patients with brain diseases and spinal cord diseases which are characterized by an excessively synchronized neuronal activity, certain spatial time stimulation patterns determined non-invasively, in particular the “Coordinated Reset” stimulation (CR stimulation) are applied in order to achieve a permanent relief. The non-invasive CR stimulation can be realized by means of different stimulation modes:
(i) by way of sensory stimulation, this means by way of physiological stimulation of receptors, such as e.g. acoustic stimulation of the inner ear, visual stimulation of the retina or mechanical stimulation (e.g. vibro-tactile stimulation) or thermal stimulation of skin receptors, subcutaneous receptors, muscle receptors and tendon receptors.
(ii) by way of stimulating peripheral nerves (and the associated receptors) e.g. by way of electric current (e.g. transcutaneous electro-stimulation) by means of magnetic fields (transdermal magnetic stimulation) or by means of ultrasound; and
(iii) by way of stimulation of the brain or spinal cord, e.g. by way of electrical current (e.g. external cranial respectively transcranial nerve stimulation), by means of magnetic fields (e.g. transcranial magnetic stimulation) or by means of ultrasound.
For the treatment of chronic subjective tonal respectively narrow band tinnitus, the acoustic CR stimulation is used. For this purpose therapeutic sounds are matched to the dominant sound of the tinnitus and are applied in the sense of the CR stimulation in order to achieve a prolonged desynchronization of the pathological synchronous activity significantly outlasting a switching off of the simulation respectively even achieve a continuous desynchronization of the pathological synchronous activity. The acoustic CR stimulation for the treatment of the tinnitus brings about a significant and markedly pronounced decrease of the symptoms (cf. P. A. Tass, I. Adamchic, H.-J. Freund, T. von Stackelberg, C. Hauptmann: Counteracting tinnitus by acoustic coordinated reset neuromodulation. Restorative Neurology and Neuroscience 30, 137-159 (2012)), a significant reduction of the pathological neuronal synchronization in a network of auditory and non-auditory regions of the brain (cf. P. A. Tass, I. Adamchic, H.-J. Freund, T. von Stackelberg, C. Hauptmann: Counteracting tinnitus by acoustic coordinated reset neuromodulation. Restorative Neurology and Neuroscience 30, 137-159 (2012); I. Adamchic, T. Toth, C. Hauptmann, P. A. Tass: Reversing pathological increased EEG power by acoustic CR neuromodulation. Human Brain Mapping 35, 2099-2118 (2014)), a significant reduction of the pathological interaction between different regions of the brain in the same (cf. A. N. Silchenko, I. Adamchic, C. Hauptmann, P. A. Tass: Impact of acoustic coordinated reset neuromodulation on effective connectivity in a neural network of phantom sound. Neuroimage 77, 133-147 (2013)), as well as in different frequency ranges (cf. I. Adamchic, B. Langguth, C. Hauptmann, P. A. Tass: Abnormal brain activity and cross-frequency coupling in the tinnitus network. Frontiers in Neuroscience 8, 284 (2014)).
In an analog way Parkinson's disease can be treated by means of vibratory tactile CR stimulation. Further indications are represented by e.g. epilepsy, functional disorders following a stroke, chronic pain syndrome (by means of vibro-tactile and/or thermal CR stimulation), migraine (e.g. by means of visual CR stimulation). Furthermore, these diseases can be treated with transcranial magnetic stimulation and/or direct electrical stimulation of the brain or direct brain stimulation by means of ultrasound.
With respect to the stimulation modalities (i) to (iii) listed above for the stimulation with stimuli of reduced intensity shall be effected, reasons are listed in the following in order to avoid side effects and/or to increase the therapeutic effectiveness:
(i) Having regard to the sensory stimulation it is important to even be able to achieve the desired stimulation effect (e.g. a phase reset of the pathological synchronized oscillatory activity in the brain or spinal cord) at an as low as possible stimulation strength. E.g. hearing impaired patients have to be treated typically with respect to the acoustic CR stimulation for the treatment of the tinnitus. The stimulation with loud sounds can damage the inner ear, complicate the communication with others as well as cover up warning signals (e.g. a vehicle horn, bicycle bell) or be perceived by the patient as being markedly unpleasant as a consequence of the threshold running fairly close to the hearing threshold considered as unbearable and the loud stimulation can also be heard by the environment of the patient and thus can be perceived as annoying. Having regard to the visual CR stimulation, in particular unpleasant blinding effects can be brought about having respect to migraine patients. Having regard to the mechanical stimulation, e.g. vibrato-tactile or thermal CR stimulation of patients with chronical pain syndrome (e.g. Morbus Sudeck or neuralgia). Even the slightest of touches or warmth stimuli can be perceived as unpleasant or even as painful. When in such cases e.g. a treatment has to be performed via the contralateral extremity or via half of the face or half of the body, the effect of stimulation as a consequence of the application in the healthy half of the body is not strongly pronounced. As a whole it is very advantageous with respect to the sensory CR stimulation when a stimulation having a very small stimulation strength can be carried out, as sensory stimuli (e.g. sounds, brightness deviations of transmission pair of glasses etc.) can interfere with the physiological processing of stimuli.
(ii) In order to be able to stimulate the peripheral nerves in an as focal manner as possible during the electric or magnetic stimulation and in order to avoid side effects that are brought about by way of the co-stimulation of adjacent structures (e.g. muscle contraction, pain sensation etc.) it is important to use as small as possible stimulation strengths.
(iii) Both the electrical and also the magnetic stimulation of the brain or spinal cord are not very focal. In particular the direct electric stimulation of the brain itself in the most favorable case of the stimulation over a plurality of small electrodes and on use of head models demanding in effort and cost besides a focal strong stimulation also lead to a co-stimulation of extensive regions of the brain that particularly for chronic irritation should be avoided or reduced without fail. In the same way the ultrasound stimulation should be limited to the actual target regions in the brain.
In all of these cases it is thus required to treat using an as small as possible stimulation strength in order to reduce the undesired co-stimulation of non-target regions. This however frequently leads thereto that the treatment is not sufficiently effective.
Moreover, the stimulation effect should be as sustainable as possible in order to ensure the compliance, this means the cooperation and “loyalty to treatment” of the patient.